High content and high stability quercetin anti-wrinkle composition and application

Abstract

The application discloses a high-content and high-stability quercetin anti-wrinkle composition and application; the composition comprises quercetin, 4-t-butylcyclohexanol and lauroyl sarcosine isopropyl ester. Compared with the prior art, the application constructs an oily composition of 4-t-butylcyclohexanol, lauroyl sarcosine isopropyl ester and quercetin, can effectively solve the problem of difficult solubility of quercetin, and greatly improves the application convenience; the quercetin content in the composition is high, and the composition has a certain anti-wrinkle effect; 4-t-butylcyclohexanol and lauroyl sarcosine isopropyl ester have a synergistic effect on quercetin solubility; the composition can be used for preparation of a quercetin microemulsion after being compounded with other oils and fats, and has extremely high stability. Thus, the application has important application value in the field of cosmetics.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of cosmetics, and particularly relates to a high-content and high-stability quercetin anti-wrinkle composition and application. BACKGROUND

[0002] Quercetin is a natural flavonoid compound with strong biological activity, which widely exists in various fruits and vegetables, has the effects of antioxidant, anticancer, antiviral, antibacterial, anti-inflammatory, etc., and plays an important role in the clinical treatment of cancer and cardiovascular diseases. However, quercetin has poor water solubility, poor oil solubility, chemical instability and low bioavailability, which greatly limits its application. It is reported that the solubility of quercetin in water is only 0.01 mg / mL (25℃), the solubility in DMSO is 150 mg / mL (25℃), and the solubility in ethanol is 4.0 mg / mL (37℃); the industry generally uses delivery systems to improve its stability, efficacy and bioavailability, and common delivery means include liposome wrapping, cyclodextrin wrapping, supramolecular co-crystals, etc.

[0003] The patent with the application number 202310059574.5, "Bacteriostatic and acne-removing microemulsion containing plant extract and preparation method thereof", mentions a quercetin microemulsion system, in which the content of quercetin is 0-1.7% of the mixture B (camellia oil, Tween 85, co-surfactant), the content is relatively low, and the co-surfactant used is ethanol, 1,2-propanediol and other polyols with relatively strong irritation; similarly, the patent with the application number 202310059662.5, "Camellia oil microemulsion loaded with quercetin and oil tea saponin and preparation method thereof", the content of quercetin is only 0.51%-1.1%; the solubility of quercetin in camellia oil is less than 1 mg / g, and the surfactant used in the microemulsion system is Tween 85, and the co-surfactant used is ethanol and propylene glycol; therefore, a stable quercetin oil composition is very important, which can get rid of the restriction of surfactants and co-surfactants, and expand the application range of quercetin. SUMMARY

[0004] The present application aims at the characteristics of quercetin, i.e. poor water and oil solubility and poor stability, and provides a high-content and high-stability quercetin anti-wrinkle composition and application. 4-tert-butylcyclohexanol is a specific TRPV1 antagonist and can effectively block the burning or tingling caused by capsaicin through human body tests, thereby effectively relieving skin discomfort. Therefore, 4-tert-butylcyclohexanol is generally used as a soothing ingredient in the cosmetic field, and the addition amount is very low. In the process of researching the quercetin dissolution system, it is found that 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester can significantly improve the solubility of quercetin, which has never been reported. Based on this, a high quercetin content oily composition is constructed, and the application potential in the cosmetic field is investigated.

[0005] The purpose of the present application is achieved by the following technical solutions.

[0006] The present application relates to a quercetin composition comprising quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester.

[0007] As an embodiment of the present application, quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester are heated to dissolve quercetin and 4-tert-butylcyclohexanol, and the quercetin composition is obtained.

[0008] As an embodiment of the present application, quercetin in the quercetin composition does not precipitate. The amount of 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester can be any amount that allows quercetin in the quercetin composition to not precipitate, based on 1 part by weight of quercetin. The no precipitation also includes no precipitation under the condition of 0℃-room temperature. In the system of the present application, the addition of 4-tert-butylcyclohexanol can allow the system to effectively dissolve quercetin with less lauroyl sarcosine isopropyl ester.

[0009] As an embodiment of the present application, the mass ratio of quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester in the composition is 1:1:4-40.

[0010] As an embodiment of the present application, the mass ratio of quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester in the composition is 1:0.5:6-40.

[0011] As an embodiment of the present application, the mass ratio of quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester in the composition is 1:1.5:3.5-40.

[0012] As an embodiment of the present application, the solubility of quercetin in the composition is 0.5% to 17%.

[0013] As an embodiment of the present application, the solubility of quercetin in the composition is 2.3% to 16.7%.

[0014] The present application also relates to the use of the aforementioned quercetin composition in the preparation of a medicine or a cosmetic.

[0015] As an embodiment of the present application, the cosmetic includes an antioxidant, anti-inflammatory or anti-wrinkle cosmetic.

[0016] As an embodiment of the present application, the medicine includes quercetin as at least one active substance.

[0017] As an embodiment of the present application, the medicine is an antioxidant, anticancer, antiviral, bacteriostatic or anti-inflammatory medicine.

[0018] As an embodiment of the present application, the quercetin composition is used as a cosmetic raw material in the form of a liposome or a microemulsion. In the field of cosmetics, the higher the content of quercetin is, the better the anti-wrinkle effect is within a certain concentration range. Quercetin is generally made into a liposome, a microemulsion or the like in the form of a cosmetic raw material to enter the development of cosmetics; in a microemulsion system or the like, the volume of the internal phase is an important factor affecting the particle size of the system; under the same particle size, the volume of the internal phase is determined; therefore, the higher the content of quercetin in the composition is, the greater the active substance loading in the microemulsion is, and the lower the effective concentration of the microemulsion is. From the perspective of cosmetic development, the lower the effective concentration of the quercetin microemulsion is, the lower the formulation cost is, and the higher the economic value is.

[0019] In summary, the present application constructs an oily composition of 4-tert-butylcyclohexanol, lauroyl sarcosine isopropyl ester and quercetin, which has the characteristics of high quercetin content and high stability, and has important application value in the field of cosmetics. Compared with the prior art, the present application has the following beneficial effects:

[0020] 1) effectively solves the problem of difficult solubility of quercetin, and greatly improves the application convenience;

[0021] 2) the composition has a high content of quercetin and has a certain anti-wrinkle effect.

[0022] 3) 4-tert-butylcyclohexanol and lauroyl sarcosine isopropyl ester have a synergistic effect on the solubility of quercetin;

[0023] 4) the composition has extremely high stability when compounded with other oils to prepare a quercetin microemulsion. BRIEF DESCRIPTION OF DRAWINGS

[0024] Other features, objects and advantages of the present application will become more apparent from the following detailed description of non-limiting embodiments, made with reference to the accompanying drawings:

[0025] Figure 1 Particle size distribution graph of quercetin microemulsion in application example 1. DETAILED DESCRIPTION

[0026] The present application is further illustrated by the following examples, but any example or combination thereof should not be construed as limiting the scope or implementation of the present application. Any modification or change to the technical solution of the present application made by those skilled in the art without departing from the spirit and scope of the present application shall also be included in the scope of the present application.

[0027] Unless otherwise specified in the examples, the conventional conditions or the conditions recommended by the manufacturer are used. All reagents or instruments, unless otherwise specified, are commercially available conventional products. In order to better illustrate the present application, numerous specific details are given in the following detailed description. Those skilled in the art should understand that the present application can also be implemented without some specific details. In some other examples, methods, means, instruments and steps well known to those skilled in the art are not described in detail in order to highlight the main idea of the present application.

[0028] Example 1

[0029] 0.5 g of quercetin, 0.5 g of 4-tert-butylcyclohexanol, and 20 g of isopropyl lauroyl sarcosinate were added to a beaker, heated and stirred until dissolved uniformly; cooled to room temperature to form a brown yellow transparent liquid, which was placed at 3℃ for 24 h without precipitation; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: isopropyl lauroyl sarcosinate was 1:1:40.

[0030] Example 2

[0031] 0.5 g of quercetin, 0.5 g of 4-tert-butylcyclohexanol, and 10 g of isopropyl lauroyl sarcosinate were added to a beaker, heated and stirred until dissolved uniformly; cooled to room temperature to form a brown yellow transparent liquid, which was placed at 3℃ for 24 h without precipitation; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: isopropyl lauroyl sarcosinate was 1:1:20.

[0032] Example 3

[0033] 0.5 g of quercetin, 0.5 g of 4-tert-butylcyclohexanol, and 5 g of isopropyl lauroyl sarcosinate were added to a beaker, heated and stirred until dissolved uniformly; cooled to room temperature to form a brown yellow transparent liquid, which was placed at 3℃ for 24 h without precipitation; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: isopropyl lauroyl sarcosinate was 1:1:10.

[0034] Example 4

[0035] 0.5 g quercetin, 0.5 g 4-tert-butylcyclohexanol, 3 g lauroyl sarcosine isopropyl ester were added into a beaker, heated and stirred until dissolved uniformly; cooled to room temperature, it was a brown yellow transparent liquid, no precipitation at 3°C for 24 h; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:1:6.

[0036] Example 5

[0037] 0.5 g quercetin, 0.5 g 4-tert-butylcyclohexanol, 2 g lauroyl sarcosine isopropyl ester were added into a beaker, heated and stirred until dissolved uniformly; cooled to room temperature, it was a brown yellow transparent liquid, no precipitation at 3°C for 24 h; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:1:4.

[0038] Example 6

[0039] 0.5 g quercetin, 0.5 g 4-tert-butylcyclohexanol, 1.5 g lauroyl sarcosine isopropyl ester were added into a beaker, heated and stirred, but not completely dissolved, the solution was turbid and not transparent; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:1:3. Compared with Examples 1-5, when the addition amount of quercetin and 4-tert-butylcyclohexanol was 1 part respectively, lauroyl sarcosine isopropyl ester needed to be added at least 4 parts to make the system transparent, and quercetin did not precipitate.

[0040] Example 7

[0041] 0.5 g quercetin, 0.25 g 4-tert-butylcyclohexanol, 3 g lauroyl sarcosine isopropyl ester were added into a beaker, heated and stirred until dissolved uniformly; cooled to room temperature, it was a brown yellow transparent liquid, no precipitation at 3°C for 24 h; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:0.5:6.

[0042] Example 8

[0043] 0.5 g quercetin, 0.25 g 4-tert-butylcyclohexanol, 2 g lauroyl sarcosine isopropyl ester were added into a beaker, and after heating and stirring, they could not be completely dissolved, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:0.5:4. Compared with Example 7, when the addition amounts of quercetin and 4-tert-butylcyclohexanol were 1 part and 0.5 part respectively, lauroyl sarcosine isopropyl ester needed to be added at least 6 parts to make the system transparent, and quercetin did not precipitate; compared with Example 5, it can be known that in the system of the present application (containing lauroyl sarcosine isopropyl ester), the addition amount of 4-tert-butylcyclohexanol will affect the stability of the system, and the higher the addition amount, the greater the solubility of the system to quercetin. In addition, it should be pointed out that the melting point of 4-tert-butylcyclohexanol is 62-70°C, and without lauroyl sarcosine isopropyl ester, if added alone, the system is solid after cooling down, not liquid.

[0044] Example 9

[0045] 0.5 g quercetin, 0.75 g 4-tert-butylcyclohexanol, 2 g lauroyl sarcosine isopropyl ester were added into a beaker, and after heating and stirring, they could not be completely dissolved, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:1.5:4.

[0046] Example 10

[0047] 0.5 g quercetin, 0.75 g 4-tert-butylcyclohexanol, 1.75 g lauroyl sarcosine isopropyl ester were added into a beaker, and after heating and stirring, they could not be completely dissolved, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:1.5:3.5.

[0048] Example 11

[0049] 0.5 g quercetin, 0.75 g 4-tert-butylcyclohexanol, 1.5 g lauroyl sarcosine isopropyl ester were added into a beaker, and after heating and stirring, they could not be completely dissolved, and the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butylcyclohexanol: lauroyl sarcosine isopropyl ester was 1:1.5:3. Compared with Example 10, when the addition amounts of quercetin and 4-tert-butylcyclohexanol were 1 part and 1.5 parts respectively, lauroyl sarcosine isopropyl ester needed to be added at least 3.5 parts to make the system transparent, and quercetin did not precipitate.

[0050] Comparative Example 1

[0051] 0.5g quercetin, 3.0g lauroyl sarcosine isopropyl ester were added into a beaker, after heating and stirring, it could not be completely dissolved, the solution was turbid and opaque; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester was 1:0:6. Compared with example 4, example 7, it can be obviously known that 4-tert-butyl cyclohexanol has a synergistic effect on the system, which is better than lauroyl sarcosine isopropyl ester alone.

[0052] Comparative example 2

[0053] 0.5g quercetin, 4.0g lauroyl sarcosine isopropyl ester were added into a beaker, after heating and stirring, it could be completely dissolved; after cooling to room temperature, it was a transparent brown yellow liquid, and no precipitation was observed after standing at 3℃ for 24h; at this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: lauroyl sarcosine isopropyl ester was 1:0:8. Compared with example 5, example 7, comparative example 1, it can be known that the addition of 4-tert-butyl cyclohexanol can realize effective dissolution of quercetin with less lauroyl sarcosine isopropyl ester.

[0054] Comparative example 3

[0055] 0.5g quercetin, 10g ethylhexyl glycerin were added into a beaker, after heating and stirring, it could not be completely dissolved, the solution was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: ethylhexyl glycerin was 1:0:10; compared with example 3, comparative example 2, it can be known that ethylhexyl glycerin is not enough to realize effective dissolution of quercetin, which side confirms the superiority of lauroyl sarcosine isopropyl ester, 4-tert-butyl cyclohexanol system.

[0056] Comparative example 4

[0057] 0.5g quercetin, 5g diisopropyl adipate were added into a beaker, after heating and stirring, it could not be completely dissolved, the solution was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: diisopropyl adipate was 1:0:10; compared with example 3, comparative example 2, it can be known that diisopropyl adipate is not enough to realize effective dissolution of quercetin, which side confirms the superiority of lauroyl sarcosine isopropyl ester, 4-tert-butyl cyclohexanol system.

[0058] Comparative example 5

[0059] 0.5g quercetin, 5g phenylpropanol were added into a beaker, after heating and stirring, it could not be completely dissolved, the solution was turbid and opaque. At this time, the ratio of quercetin: 4-tert-butyl cyclohexanol: phenylpropanol was 1:0:10; compared with example 3, comparative example 2, it can be known that phenylpropanol is not enough to realize effective dissolution of quercetin, which side confirms the superiority of lauroyl sarcosine isopropyl ester, 4-tert-butyl cyclohexanol system.

[0060] Application example

[0061] Referring to the low-temperature emulsification method in patent application number 202211695584.X, entitled "A Microemulsion and Its Preparation Method", a system of quercetin, lauroyl sarcosine isopropyl ester, 4-tert-butylcyclohexanol and tocopheryl acetate and other oils can be compounded and used in the preparation of microemulsions. The detailed process is as follows:

[0062] Weigh 2g of quercetin, 2g of 4-tert-butylcyclohexanol, 16g of lauroyl sarcosine isopropyl ester, and 4g of tocopheryl acetate into a 100mL beaker, heat and stir until dissolved and homogeneous, and record this as the oil phase. Weigh 20g of PPG-13-decyltetradecyl alcohol polyether-24 and 24g of glycerol into a 150mL beaker, turn on mechanical stirring, and stir at 300rpm for 10min until homogeneous. Then add the oil phase into the beaker in three batches and stir for 30min until homogeneous to obtain the microemulsion premix. Then add the microemulsion premix to 32g of water, stir the resulting gel block until homogeneous to obtain the microemulsion. The microemulsion is clear and transparent and no precipitation occurs after centrifugation at 9000rpm for 10min.

[0063] The particle size was determined using a Bettersize 3000 particle size analyzer. Figure 1 The average particle size D50 was 84 nm. Its one-month stability under different conditions was investigated, as detailed in Table 1. Table 1 shows that the quercetin content in the microemulsion decreased by 12.6% under light irradiation, while the quercetin content remained almost unchanged under other conditions. This indicates that the quercetin microemulsion exhibits excellent stability and has great application potential in the cosmetics field. It should be noted that this application example is intended to illustrate the value of the composition in the cosmetics field, specifically in the microemulsion field. Furthermore, in this application example, if 2g of quercetin, 16g of lauroyl sarcosine isopropyl ester, and 4g of tocopheryl acetate are used, quercetin will precipitate out under this ratio.

[0064] Table 1 shows the quercetin content in the samples after one month.

[0065] Item -18℃ 3℃ 40℃ 48℃ High and low temperature cycles Light Room temperature Quercetin content 2.083 2.099 2.014 2.022 2.014 1.748 1.958

[0066] Efficacy test example

[0067] The anti-wrinkle efficacy of the solution from Example 3 was tested, as detailed below:

[0068] Skin fibroblasts in the logarithmic growth phase were seeded into 3 cm diameter cell culture dishes or 6-well cell culture plates. After the cells reached 80% confluence, different concentrations of culture medium were added to the sample groups for culture. Normal culture medium was added to the blank control wells and cultured for another 24 hours. The cell supernatant was collected and the content of type I collagen was detected using an ELISA kit.

[0069] Table 2 Collagen promotion test results

[0070] Product name Concentration Relative value of collagen type I Remarks Normal control / 100.00％ Blank control TGF 50 ng / ml 143.87％ Positive control Oily composition 0.01％ 117.27％ Sample

[0071] As can be seen from Table 2, the oily composition of 4-tert-butylcyclohexanol, lauroylsarcosine isopropyl ester, and quercetin has a significant promotion effect on type I collagen and has a certain anti-wrinkle effect.

[0072] The specific embodiments of the present application are described above. It needs to be understood that the present application is not limited to the specific embodiments described above, and various modifications or changes can be made by those skilled in the art within the scope of the claims, which does not affect the essential content of the present application.

Claims

1. A quercetin composition comprising quercetin, 4-tert-butylcyclohexanol, and lauroylsarcosine isopropyl ester; wherein, The mass ratio of quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropryl ester is 1:1:4-40; or, the mass ratio of quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropryl ester is 1:0.5:6-40; or, the mass ratio of quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropryl ester is 1:1.5:3.5-40.

2. The quercetin composition of claim 1, wherein, The quercetin, 4-tert-butylcyclohexanol and lauroyl sarcosine isopropryl ester are heated until the quercetin and 4-tert-butylcyclohexanol are dissolved, to obtain the quercetin composition.

3. The quercetin composition of claim 1, wherein, The solubility of quercetin in the composition is 0.5%-17%.

4. The quercetin composition of claim 1, wherein, The solubility of quercetin in the composition is 2.3%-16.7%.

5. Use of the quercetin composition according to any one of claims 1-4 in the preparation of a medicine or a cosmetic.

6. Use according to claim 5, characterized in that, The quercetin composition is used as a cosmetic raw material in the form of a liposome or a microemulsion.

7. Use according to claim 5, characterized in that, The cosmetic includes an antioxidant, anti-inflammatory or anti-wrinkle cosmetic. The cosmetic includes an antioxidant, anti-inflammatory or anti-wrinkle cosmetic.

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